Добірка наукової літератури з теми "NEURO-OLFACTORY SYSTEM"

Topoisomerase IIIβ (Top3β), the only dual-activity topoisomerase in mammals that can change topology of both DNA and RNA, is known to be associated with neurodevelopment and mental dysfunction in humans. However, there is no report showing clear associations of Top3β with neuropsychiatric phenotypes in mice. Here, we investigated the effect of Top3β on neuro-behavior using newly generated Top3β deficient (Top3β−/−) mice. We found that Top3β−/− mice showed decreased anxiety and depression-like behaviors. The lack of Top3β was also associated with changes in circadian rhythm. In addition, a clear expression of Top3β was demonstrated in the central nervous system of mice. Positron emission tomography/computed tomography (PET/CT) analysis revealed significantly altered connectivity between many brain regions in Top3β−/− mice, including the connectivity between the olfactory bulb and the cerebellum, the connectivity between the amygdala and the olfactory bulb, and the connectivity between the globus pallidus and the optic nerve. These connectivity alterations in brain regions are known to be linked to neurodevelopmental as well as psychiatric and behavioral disorders in humans. Therefore, we conclude that Top3β is essential for normal brain function and behavior in mice and that Top3β could be an interesting target to study neuropsychiatric disorders in humans.

Biologically inspired to mammalian olfactory system, electronic noses became popular during the last three decades. In literature, as well as in daily practice, a wide range of applications are reported. Nevertheless, the most pioneering one has been (and still is) the assessment of the human breath composition. In this study, we used a prototype of electronic nose, called Wize Sniffer (WS) and based it on an array of semiconductor gas sensor, to detect ammonia in the breath of patients suffering from severe liver impairment. In the setting of severely impaired liver, toxic substances, such as ammonia, accumulate in the systemic circulation and in the brain. This may result in Hepatic Encephalopathy (HE), a spectrum of neuro–psychiatric abnormalities which include changes in cognitive functions, consciousness, and behaviour. HE can be detected only by specific but time-consuming and burdensome examinations, such as blood ammonia levels assessment and neuro-psychological tests. In the presented proof-of-concept study, we aimed at investigating the possibility of discriminating the severity degree of liver impairment on the basis of the detected breath ammonia, in view of the detection of HE at its early stage.

The number of deaths has been increased due to COVID-19 infections and uncertain neurological complications associated with the central nervous system. Post-infections and neurological manifestations in neuronal tissues caused by COVID-19 are still unknown and there is a need to explore how brainstorming promoted congenital impairment, dementia, and Alzheimer’s disease. SARS-CoV-2 neuro-invasion studies in vivo are still rare, despite the fact that other beta-coronaviruses have shown similar properties. Neural (olfactory or vagal) and hematogenous (crossing the blood–brain barrier) pathways have been hypothesized in light of new evidence showing the existence of SARS-CoV-2 host cell entry receptors into the specific components of human nerve and vascular tissue. Spike proteins are the primary key and structural component of the COVID-19 that promotes the infection into brain cells. Neurological manifestations and serious neurodegeneration occur through the binding of spike proteins to ACE2 receptor. The emerging evidence reported that, due to the high rate in the immediate wake of viral infection, the olfactory bulb, thalamus, and brain stem are intensely infected through a trans-synaptic transfer of the virus. It also instructs the release of chemokines, cytokines, and inflammatory signals immensely to the blood–brain barrier and infects the astrocytes, which causes neuroinflammation and neuron death; and this induction of excessive inflammation and immune response developed in more neurodegeneration complications. The present review revealed the pathophysiological effects, molecular, and cellular mechanisms of possible entry routes into the brain, pathogenicity of autoantibodies and emerging immunotherapies against COVID-19.

Female sexual behavior is under the complex influence of psycho-emotional, neuroendocrine and social factors. The realization of normal sexual activity in women is possible if many conditions are met and, first of all, ensuring a positive psycho-emotional background, safety, a satisfactory state of health, as well as comfortable interpersonal relationships for most women. In addition to significant psychological and social impact, accumulated modern scientific data confirm the important role of neuro-hormonal regulation of sexual behavior and suggest the potential effectiveness of pharmacological therapy. Unfortunately, however, medical strategies for correcting female sexual disorders are limited. Currently, in some countries, several drugs that increase female sexual activity are allowed for use, however, all of them are not registered and are not approved for use on the territory of the Russian Federation. The article briefly describes the neural mechanisms of the main areas of the central nervous system underlying receptivity and sexual attraction, namely the olfactory and limbic systems, the neocortex. The main attention is paid to the function of neurotransmitters and hormones that are critically involved in the modulation of emotions and sexual behavior, including the inhibitory mediator of gamma aminobutyric acid (GABA), estrogens, testosterone, and the excitatory mediator glutamate. The stages of development, the results of experimental and clinical studies to assess the effectiveness and safety of the unique Russian neuropeptide drug Desirex, which is a stimulant of sexual behavior due to the mechanism of reversible suppression of the GABAergic system, nonspecific stimulation of the dopaminergic system of motivation and reinforcement of positive emotions and disinhibition of the controlling function of the neocortex, are presented in detail.

In this review, recent studies using pharmacological treatment, cell transplantation, and gene therapy to promote regeneration of the injured spinal cord in animal models will be summarized. Pharmacological and cell transplantation treatments generally revealed some degree of effect on the regeneration of the injured ascending and descending tracts, but further improvements to achieve a more significant functional recovery are necessary. The use of gene therapy to promote repair of the injured nervous system is a relatively new concept. It is based on the development of methods for delivering therapeutic genes to neurons, glia cells, or nonneural cells. Direct in vivo gene transfer or gene transfer in combination with (neuro)transplantation (ex vivo gene transfer) appeared powerful strategies to promote neuronal survival and axonal regrowth following traumatic injury to the central nervous system. Recent advances in understanding the cellular and molecular mechanisms that govern neuronal survival and neurite outgrowth have enabled the design of experiments aimed at viral vector-mediated transfer of genes encoding neurotrophic factors, growth-associated proteins, cell adhesion molecules, and antiapoptotic genes. Central to the success of these approaches was the development of efficient, nontoxic vectors for gene delivery and the acquirement of the appropriate (genetically modified) cells for neurotransplantation. Direct gene transfer in the nervous system was first achieved with herpes viral and E1-deleted adenoviral vectors. Both vector systems are problematic in that these vectors elicit immunogenic and cytotoxic responses. Adeno-associated viral vectors and lentiviral vectors constitute improved gene delivery systems and are beginning to be applied in neuroregeneration research of the spinal cord. Ex vivo approaches were initially based on the implantation of genetically modified fibroblasts. More recently, transduced Schwann cells, genetically modified pieces of peripheral nerve, and olfactory ensheathing glia have been used as implants into the injured spinal cord.

Diseases affecting the central nervous system (CNS) are among the most disabling and the most difficult to cure due to the presence of the blood–brain barrier (BBB) which represents an impediment from a therapeutic and diagnostic point of view as it limits the entry of most drugs. The use of biocompatible polymer nanoparticles (NPs) as vehicles for targeted drug delivery to the brain arouses increasing interest. However, the route of administration of these vectors remains critical as the drug must be delivered without being degraded to achieve a therapeutic effect. An innovative approach for the administration of drugs to the brain using polymeric carriers is represented by the nose-to-brain (NtB) route which involves the administration of the therapeutic molecule through the neuro-olfactory epithelium of the nasal mucosa. Nasal administration is a non-invasive approach that allows the rapid transport of the drug directly to the brain and minimizes its systemic exposure. To date, many studies involve the use of polymer NPs for the NtB transport of drugs to the brain for the treatment of a whole series of disabling neurological diseases for which, as of today, there is no cure. In this review, various types of biodegradable polymer NPs for drug delivery to the brain through the NtB route are discussed and particular attention is devoted to the treatment of neurological diseases such as Glioblastoma and neurodegenerative diseases.

In mammals, the accessory olfactory system is a distinct circuit that has received attention for its role in detecting and responding to pheromones. While the neuroscientific investigation of this system is comparatively new, recent advances and its compact size have made it an attractive model for developing an end-to-end understanding of such questions as regulation of essential behaviors, plasticity, and individual recognition. Recent discoveries have indicated a need to reevaluate our conception of this system, suggesting that ( a) physical principles—rather than biological necessity—play an underappreciated role in its raison d'être and that ( b) the anatomy of downstream projections is not dominated by unique specializations but instead consists of an abbreviated cortical/basal ganglia motif reminiscent of other sensorimotor systems. These observations suggest that the accessory olfactory system distinguishes itself primarily by the physicochemical properties of its ligands, but its architecture is otherwise a microcosm of mammalian neurocircuitry.

La pollution atmosphérique est un problème majeur de santé publique. Parmi ses composants, les particules fines et ultrafines émises par les moteurs diesel sont aujourd’hui très critiquées. En effet, ces particules sont capables de gagner le système circulatoire et atteindre divers organes et, dans une certaine mesure, le cerveau. Si leur neurotoxicité est fortement suspectée dans les populations directement exposées, les conséquences d’une exposition maternelle sur la mise en place et le maintien des circuits neuronaux de la descendance restent mal connues. Des études épidémiologiques et expérimentales soulignent les risques neurotoxiques liés à l’exposition gestationnelle, du fait de la fragilité du cerveau en développement. Néanmoins, les conséquences d’une telle exposition sur le neurodéveloppement du fœtus et de l’individu après la naissance sont peu étudiées dans des conditions de faible exposition contrôlée et répétée. Cette thèse a visée à étudier les effets neurotoxiques à court et long terme d’une exposition gestationnelle aux fumées de moteur diesel enrichies en particules fines dans des conditions mimant l’exposition humaine. Ce travail a été mené chez le lapin, un modèle animal de la placentation humaine. Il s’est focalisé sur la description des atteintes sur le continuum anatomo-fonctionnel entre système olfactif et cerveau par des approches comportementales, neurochimiques et histologiques chez le fœtus en fin de gestation et chez l’adulte. Au stade fœtal, les résultats suggèrent la présence d'amas de particules de taille nanométrique sans que leur nature soit déterminée dans les tissus olfactifs des animaux exposés, une désorganisation cellulaire de ces tissus et des atteintes neurochimiques localisées au niveau du bulbe olfactif et dans certaines régions du cerveau pour la transmission dopaminergique et sérotoninergique, suggérant une dénervation des systèmes neuromodulateurs bulbaires en provenance du système nerveux central. A la naissance, une modification de la sensibilité olfactive périnatale chez les lapereaux en réponse à la phéromone mammaire, dont la perception est essentielle au déclenchement du comportement de tétée, a été observée et suggère une modification des réseaux nerveux des individus issus de mères exposées. Les perturbations neurochimiques persistent à long terme, malgré peu d’impact sur les comportements à base olfactive. De façon intéressante, un effet différentiel de ce type d’exposition selon le sexe est observé sur les systèmes monoaminergiques des fœtus et adultes. L’ensemble des données décrites ici indique un potentiel neurotoxique à confirmer et souligne la nécessité d'investiguer de façon plus approfondie l'éventuel lien avec l’émergence des maladies neurodégénératives humaines. Ces données confirment que la phase prénatale doit être considérée comme une fenêtre importante pour le développement du cerveau, au cours de laquelle il existe une susceptibilité élevée aux agressions de l'environnement
Airborne pollution is a major public health concern. Among its components, the fine and ultrafine particles emitted by diesel engines are highly criticized. Indeed, these particles are able to gain the circulatory system to reach various organs and, in a certain degree, the brain. If their neurotoxicity is highly suspected in directly exposed populations, the consequences of maternal exposure on both fetal brain maturation and neurobehavioral development after birth remain poorly understood. Several recent studies conducted on humans or animal models have highlighted neurotoxic risks related to gestational exposure, due to the fragility of the brain at such critical period for its anatomic and functional development. Nevertheless, the consequences of maternal exposure on fetal brain maturation and neurobehavioral development after birth remain poorly understood in conditions of controlled and repeated low exposure. The aim of the thesis was to study the short- and long-term neurotoxic effects of gestational exposure to diesel engine fumes enriched with fine particles in conditions mimicking human exposure. The work was conducted in rabbit, because of its hemodichorial placentation which is anatomically and functionally close to that in humans. It focused on describing the damages to the anatomical and functional continuum between the olfactory system and the brain using behavioral, neurochemical and histological approaches in the late fetus and in adults. The results suggest the presence of chemically undefined nanosized particles in fetal olfactory tissues of exposed animals and a cellular disorganization of the same tissues, which is associated to localized neurochemical damage in the olfactory bulb and in several regions of the brain involved in dopaminergic and serotoninergic transmission, suggesting a denervation of centrifugal bulbar neuromodulatory systems from the central nervous system. At birth, a modulation in perinatal olfactory sensitivity in rabbits in response to the mammary pheromone, the perception of which is essential to trigger feeding behavior, is observed, suggesting a modification of the nervous networks of in utero exposed individuals. Neurochemical disturbances persist in adults, despite little impact on olfactory-based behaviors. Interestingly, a sex-dependent differential effect of this type of exposure on monoaminergic systems is observed in fetuses and adults. We propose that these neurodevelopmental perturbations of the anatomo-functional continuum between the olfactory system and the brain may indicate a neurotoxic potential and underline the need to further investigate its eventual link with the emergence of human neurodegenerative diseases. These data confirmed that prenatal phase should be considered as an important window for brain development, during which there is an elevated susceptibility to environmental insults

Mosquitoes are the deadliest animals in the world and responsible for transmitting a variety of infectious disease such as malaria, dengue fever, chikungunya, zika fever. Among them, malaria which is transmitted by Anopheles mosquitoes is one of the major vector-borne diseases that cause millions of mortality and morbidity worldwide. Continuous climate change, global warming, and other environmental factors are the facilitators of mosquito population growth and thus worse the situation of mosquitoborne diseases. Current tools to control and manage malaria face challenges due to the emergence of parasite resistance to antimalarial drugs and insecticide resistance of mosquitoes. Thus, alternative approaches are needed for the global elimination of malaria. Evolution and adaptation of blood feeding behavior of adult female mosquitoes not only favored their reproductive success but also make them an important disease vectors. Mosquitoes rely extensively on their sense of smell (olfaction) for the majority of their lifecycle stages and the well-developed nasal system plays an essential role in the facilitation of olfactory guided behavior. Thus, decoding the genetic relationship of the neuro-olfactory system managing host seeking and blood feeding behavioral responses of adult female mosquitoes, may provide an opportunity to design new molecular strategy to disrupt human-mosquito interactions. Our RNA-Seq analysis of the neuro-olfactory system of Anopheles culicifacies mosquito, which transmit more than 65% malaria cases in rural India, unravelled that a tight coordination of the olfactory and the central nervous system is necessary to regulate the ‘pre and post’ blood meal associated with complex behavioral responses such as host-seeking, blood feeding, and oviposition. A comprehensive molecular cataloging and comparative gene expression analysis of the olfactory tissue transcriptome data indicated that synergetic actions of the olfactory encoded molecular factors (Odorants Binding Proteins and Olfactory receptors) facilitate and manage the complex host-seeking behavioral events. Next, transcriptional profiling of the selected olfactory transcripts in two consecutive blood feeding experiment highlighted that adult female mosquitoes might learn and memorize from the priming effect of the first blood meal exposure, which further facilitates host selection and rapid blood meal uptake during second blood feeding event. Furthermore, species-specific transcriptional profiling and an in-silico analysis of novel ‘sensory appendages proteins’ revealed their potential role in host-seeking and blood feeding behavior, possibly a unique target for functional characterization and designing of molecular strategy for the control of An. culicifacies mosquitoes. Our comparative vi RNA-Seq analysis of naïve and blood fed adult female mosquitoes brain unraveled that a gradual modulation of brain transcripts expression is crucial to regulate the complex events linked to metabolic switch activities such as blood meal digestion, egg maturation, oviposition etc. Finally, the characterization of two olfactory-specific proteins Quick-to-Court and Attractin provide a new knowledge that how mosquitoes manage the conflicting demand of mating vs. blood feeding.